1. Field of the Invention
The present invention relates to a microscope system that acquires a specimen image by capturing a specimen using a microscope, displays the acquired specimen image, and observes the specimen, and also relates to a specimen observing method, and a computer-readable recording medium.
2. Description of Related Art
For example, in pathological diagnosis, a system that creates a specimen by thinly slicing a tissue specimen obtained by removing an organ or performing a needle biopsy with the thickness of approximately several micrometers and performs a magnifying observation using an optical microscope for acquiring various findings has been widely performed. In this case, since the specimen rarely absorb and scatter any light and is nearly clear and colorless, the specimen is generally stained by a pigment before the observation.
Conventionally, various types of staining methods have been suggested. However, regarding especially the tissue specimen, hematoxylin eosin staining (hereinafter, referred to as “HE staining”) using two pigments of hematoxylin and eosin is generally used as morphological observation staining for a morphological observation of the specimen. For example, a method that captures the specimen subjected to the HE staining with multi-bands, estimates a spectral spectrum of a specimen position to calculate (estimate) the pigment amount of the pigment staining the specimen, and synthesizes R, G, and B images for display is disclosed (for example, see Japanese Laid-open Patent Publication No. 2008-51654, Japanese Laid-open Patent Publication No. 7-120324, and International Publication No. 00/06774). As another morphological observation staining, for example, in cytological diagnosis, Papanicolaou staining (Pap staining) is known.
In the pathological diagnosis, molecule target staining to confirm an expression of molecule information is performed on the specimen to be used for diagnosis of function abnormality, such as expression abnormality of a gene or a protein. For example, the specimen is fluorescently labeled using an IHC (immunohistochemistry) method, an ICC (immunocytochemistry) method, and an ISH (in situ hybridization) method and fluorescently observed, or is enzyme-labeled and observed in a bright field. In this case, in the fluorescent observation of the specimen by the fluorescent labeling, for example, a confocal laser microscope is used. In this observation using the fluorescent labeling, highly-sensitive sharp image can be obtained, so that the specimen can be observed three-dimensionally, or the specimen can be observed in a desired direction. Further, there is an advantage in that a plurality of target molecules (antigen) can be labeled at a time.
Meanwhile, in the bright field observation (the IHC method, the ICC method, and a CISH method) by the enzyme labeling, an optical microscope is used, and therefore, the observation can be performed together with the morphological observation.
On the other hand, in recent years, as a treatment of cancers and the like, therapy called molecular target therapy using therapeutic agent acting on particular molecules (antibody therapeutic agent) has been carried out, and is expected to have therapeutic effect and reduce the side effects. In this cancer treatment using the molecular target therapy, antibody therapeutic agent targeted for specific molecules in cancer cells (protein antigen) is used, and before the treatment, for example, whether antigen serving as the target molecules of the antibody therapeutic agent is expressed on the surface of cells, i.e., cell membrane, is observed by the IHC method and the like, whereby patients eligible for the treatment are selected. Examples of antibody therapeutic agents approved for use include trastuzumab (Herceptin (registered trademark)), i.e., anti-HER2 antibody preparation for breast cancer, and cetuximab (Erbitux (registered trademark)), i.e., anti-EGFR antibody preparation for colorectal cancer.
Antibodies are caused to act on a plurality of target molecules (antigen) to label each antigen, a combination of presence/absence of the expressions (expression pattern) has been evaluated (antibody panel evaluation). For example, a combination of antigens expressed on a cell membrane is evaluated to identify cancer stem cells. More specifically, for example, in diagnosis of breast cancer, cells in which CD 44 molecule is expressed on the cell membrane and CD 24 molecule is not expressed on the cell membrane (or expressed at a lower level) are identified as stem cells. On the other hand, in diagnosis of colorectal cancer, cells in which CD 44 molecule and CD 133 are expressed on the cell membrane are identified as stem cells. In addition, various kinds of antibody panel evaluation are performed by exerting antibodies and labeling antigens, in accordance with purposes such as estimation of a primary source of cancer whose primary source is unknown (for example, distinguishing epithelial cancers of colon cancer, breast cancer, and lung cancer), distinguishing of B-cell lymphoma and T-cell lymphoma, identification of mesothelioma, distinguishing of squamous cell carcinoma and adenocarcinoma, and the like.
Furthermore, in breast cancer treatment in recent years, target treatment selectively using antibody therapeutic agent is making progress, and it is common practice to, depending on the expression pattern of multiple target molecules in a tumor site, classify the disease type (cell variant) into four types called “Luminal B”, “Luminal A”, “HER2 disease”, and “Basal like”, and accordingly, a treatment method is basically selected. For example, see Toru Watanabe, Rie Tahara, “Breast cancer; new disease classification and use of molecular targeted drugs”, Keiyukai, Hamamatsu Oncology Center, [retrieved on 2010-05-07] (Retrieved from the Internet <URL: http://www.cancertherapy.jp/molecule/2009_spring/06.html>) (hereinafter, referred to as Watanabe reference). For example, depending on presence or absence of expression on the cell nucleus of estrogen receptor (hereinafter abbreviated as “ER”) and progesterone receptor (hereinafter abbreviated as “PgR”), i.e., hormone receptors, a determination is made as to whether cancer multiplies depending on hormone, and a determination is made as to whether endocrine therapy (hormone therapy) is applicable or not. In addition, depending on presence or absence of expression on a cell membrane of HER2 receptor (hereinafter abbreviated as “HER2”), a selection is made as to whether trastuzumab (Herceptin (registered trademark)), i.e., anti-HER2 antibody preparation, can be applied or not. In the type called triple-negative breast cancer (TNBC) in which none of ER, PgR, HER2 expresses, chemotherapy is mainly used as treatment.
For example, when the target molecule is labeled by molecule target staining or when a plurality of target molecules are labeled by molecule target staining, the technique disclosed in Japanese Laid-open Patent Publication No. 2008-51654, Japanese Laid-open Patent Publication No. 7-120324, and International Publication No. 00/06774 is applied, so that for each pigment staining the specimen (pigment made visible by molecule target staining), the pigment amount can be calculated, and an RGB image synthesized for display can be displayed on the display device and can be observed.